CRF is a hormone composed of 41 amino acids (see Science, vol. 213, pp. 1394-1397 (1981), J. Neurosci., vol. 7, pp. 88-100 (1987)). It has been suggested that CRF plays a key role in biological reactions to stress (see Cell. Mol. Neurobiol., vol. 14, pp. 579-588 (1994), Endocrinol., vol. 132, pp. 723-728 (1994), and Neuroendocrinol., vol. 61, pp. 445-452 (1995)). CRF functions through two routes; a route through the hypothalamo-hypophysial-adrenal system for acting on the peripheral immune system and the sympathetic nervous system, and a route through the central nervous system in which it functions as a neurotransmitter (see Corticotropin Releasing Factor: Basic and Clinical Studies of a Neuropeptide, pp. 29-52 (1990)) CRF intracerebroventicularly administered to hypophysectomized rats and normal rats induces anxiety-like symptoms in both rats (see Pharmacol. Rev., vol. 43, pp. 425-473 (1991) and Brain Res. Rev., vol. 15, pp. 71-100 (1990)). That is, CRF is believed to participate in the hypothalamo-hypophysial-adrenal system and to function as a neurotransmitter in the CNS.
As Owens and Nemeroff collected in Pharmacol. Rev., vol. 43, pp. 425-474 (1991), diseases in which CRF takes part include depression, anxiety, Alzheimer's disease, Parkinson's syndrome, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug dependence, inflammation, and immunity-associated diseases. It has recently been reported that CRF is also involved in epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, and head wounds (see Brain Res., vol. 545, pp. 339-342 (1991), Ann. Neurol., vol. 31, pp. 48-498 (1992), Dev. Brain Res., vol. 91, pp. 245-251 (1996), and Brain Res., vol. 744, pp. 166-170 (1997)). Therefore, an antagonist against a CRF receptor is useful as a treating agent for these diseases.
An object of the invention is to provide a CRF receptor antagonist effective as a treating agent or a prophylactic agent for diseases in which CRF is said to participate, such as depression, anxiety, Alzheimer's disease, Parkinson's syndrome, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head wounds, inflammation, and immunity-associated diseases.